Animal models have demonstrated that T cells stimulated with both anti- CD3 and interleukin-2 (IL-2) are effective against a variety of LAK and IL-2 resistant tumor lines. In addition, these activated killer T cells (T-AK) traffic in greater numbers to tumor nodules than LAK cells. Based on these findings, and a Phase I study of anti-CD3 alone in patients with advanced malignancies, a strategy was devised to stimulate autologous lymphocytes ex vivo with anti-CD3 followed by IL-2 in vivo. To accomplish this, peripheral blood lymphocytes are obtained from patients by leukapheresis. These cells are stimulated in the lab with anti-CD3 for 12-16 hours. They are then transferred back to the patient on the following day and IL-2 is begun. The number of cells administered and the time course and dose of IL-2 varies with the assigned treatment cohort. Five cohorts have been completed with additional ones planned. An atypical lymphocytosis with a concurrent anion gap metabolic acidosis and coagulopathy as well as the previously reported renal, hepatic and neurologic toxicities with IL-2 were seen. The acidosis was severe enough to require mechanical ventilation and dialysis in one patient. No other grade IV pulmonary toxicities related directly to this protocol have been seen. Of the 30 patients treated thus for, there has been one partial and one minimal response.